Updates from the National Antimicrobial Committee (NAC) Updates 2018.pdfآ  Updates from the...

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Transcript of Updates from the National Antimicrobial Committee (NAC) Updates 2018.pdfآ  Updates from the...

  • Updates from the National Antimicrobial Committee (NAC)

    Dr. Anne-Marie Van den Abeele, AZ St Lucas, GentDr. Bndicte Lissoir, GHdC, Charleroi

    Dr. Kris Vernelen, ISP-WIV, Brussel

  • Content Fosfomycin susceptibility testing

    Trimethoprim-sulfamethoxazole and Stenotrophomonas maltophilia

    Survey satisfaction NAC panel 2016

  • Fosfomycin: introduction

    Streptomyces fradiae (1969, Spain) Low molecular weight Water soluble: good tissue diffusion Drug formulation:

    Dosage:

    - Fosfo-tromethamine/trometamol (soluble salt ) oral use- Fosfo-calcium oral use (less good bioavailability)- Fosfo-disodium salt intravenous use

    Usual dosage IV: 3x4g/dHigh dosage IV: 3x8g/d

  • Fosfomycin: spectrum of activity

    Broad spectrum activity, bactericidal (MBC MIC)

    Gram + - Staphylococcus aureus (MSSA, MRSA)- (Streptococci, Enterococci)

    Gram -- Escherichia coli- Proteus mirabilis- (K. pneumoniae, Enterobacter spp.)- Pseudomonas aeruginosa

  • Fosfomycin: resistance mechanisms

    - Plasmidic: Inactivating enzymes- Metallo enzymes: FosA, FosB, FosXtransferable

    - Kinases: FomA, FomB

    - Chromosomal: Mutations in uptake system genes(transporters: GlpT, UhpT)

    - Reduced affinity to target (MurA) (natural resistance)Staphylococcus saprophyticus, (S. capitis), Morganella morganii, Acinetobacter spp, Burkholderia cepacia, Stenotrophomonas maltophilia, Anaerobes

    ! No cross resistance with other classes of antibiotics! Resistant mutants less virulent (fitness cost)! High frequency of mutations during treatment

  • Fosfomycin AST (1)

    EUCAST (Enterobacteriaceae / Staphylococci): S < 32 g/ml; R > 32 g/ml

    CLSI (Enterobacteriaceae): S < 64 g/ml; I= 128 g/ml; R 256 g/ml

    Only urinary E. coli

    No breakpoints (Pseudomonas aeruginosa) EUCAST: potential use of ECOFF (MIC =128 mg/l) for use in combination

    therapyMiscellaneous agents MIC breakpoint

    (mg/L)Disk

    content (g)

    Zone diameter breakpoint

    (mm)

    Notes Numbered notes relate to general comments and/or MIC breakpoints. Lettered notes relate to the disk diffusion method.

    S R > S R